The Partners Healthcare Systems/Harvard Medical School/Boston Medical Center AIDS Clinical Trials Unit, previously known as the Harvard Medical School/Boston Medical Center (HMS/BMC) AIDS CTU, comprises a consortium of clinical research sites (CRS) affiliated with the AIDS Clinical Trials Group (ACTG) network leadership group. The CRSs are located at Massachusetts General Hospital (MGH), Brigham and Women's Hospital (BWH), Beth Israel-Deaconess Medical Center (BIDMC), and Boston Medical Center (BMC), with an administrative component located at MGH. Throughout its 19-year history, investigators of the HMS/BMC AIDS CTU have made major contributions to therapeutic research in AIDS and have played a critical role in the scientific leadership of the ACTG: pivotal studies demonstrating clinical efficacy of combination antiretroviral therapy, protease inhibitor therapy, and combination therapy of HCV in co-infected persons all have been led by HMS/BMC AIDS CTU investigators. We propose a comprehensive, integrated clinical and translational research program that addresses five of the six priority areas described in the Network Leadership Group RFA (AI-05-001), including: 1) translational research/drug development; 2) optimization of clinical management, including co-morbidities; 3) vaccine development (therapeutic vaccines); 4) prevention of mother-to-child transmission (in collaboration with the Boston IMPAACT Clinical Trials Unit); and 5) prevention of HIV-1 infection. In addition, the Partners/Harvard/BMC AIDS CTU has formed mentoring partnerships with the Botswana CTU in Gaborone and the Chinese Academy of Medical Sciences/Peking Union Medical College CTU in Beijing through which investigators and research staff of the Partners/Harvard/BMC AIDS CTU provide training and guidance in the conduct of ACTG trials. Recruitment of women and subjects from traditionally underrepresented minority groups is a top priority of the Partners/Harvard/BMC AIDS CTU. This goal is aided by location of two of our CRSs (BWH and BMC in predominantly minority neighborhoods, and outreach efforts coordinated with our Community Advisory Board. Results of the studies proposed in this application will have a profound impact on public health by improving clinical care, preventing or delaying HIV disease progression, and reducing or eliminating the morbidity and mortality associated with HIV-1 infection and its associated complications. ADMINISTRATIVE COMPONENT